Alzheimer’s drugs based on amyloid cascade hypothesis getting tangled up in scrutiny

One of our friends from the Collaborative on Health and the Environment recently cached a few recent Alzheimer’s drug stories online and sent word around to Peter and I, amongst others.

The articles illustrate the increasing scrutiny the amyloid cascade hypothesis has come under in the past several years, as every drug candidate has failed to produce the expected breakthrough. Here is a sampling of quotes from the stories:

“Companies said they’re running into a stone wall with Alzheimer’s and Parkinson’s,” said Ray Woosley, chief executive of the Critical Path Institute, which oversees the coalition. “We really believe drugs are failing because we honestly don’t understand the disease.” Drug Makers Will Share Data from Failed Alzheimer’s Trials, THE WALL STREET JOURNAL

“If you say Alzheimer’s, everyone immediately thinks that it’s the plaques that actually cause the disease. That couldn’t be further from the truth,” Andrew Dillin, of the Salk Institute in California and the Howard Hughes Medical Institute, told reporters in London this week at a conference on aging.

“It actually sequesters all of that amyloid,” said Adrian Ivinson, who directs the Harvard NeuroDiscovery Center in Boston, a drug discovery center affiliated with Harvard Medical School working on new Alzheimer’s drugs.

“The plaque is not the main culprit in terms of toxicity,” said Dr. Scott McGinnis of Harvard Medical School and Brigham and Women’s Hospital in Boston, who treats Alzheimer’s patients and runs clinical trials testing new Alzheimer’s drugs. A new theory of Alzheimer’s explains drug failures, THE WALL STREET JOURNAL

In the book and on the blog we — and others, such as Richard Taylor and Mona Johnson, who wrote a great article on the failing dominant hypothesis last week — have warned about reductionist approaches to AD, while asking whether it is wise to invest billions of dollars in trying to modify a few specific proteins whose role in brain aging we do not fully understand.

From the perspective of Peter and I, it is much more prudent to broaden our research models to comprehend brain aging as a lifespan issue rather than fixating on neural proteins that appear downstream. Equally important is inspiring individuals to embrace an integrative public-health approach that protects against the many insults to the human brain over a lifetime.

As a molecular geneticist friend and I just wrote in a recent letter to the editor in the journal Chemical & Engineering News, strategies that reduce vascular risk factors, minimize oxidative stress, guard against traumatic brain injuries, promote social engagement, lifelong learning, and purposeful activity, reduce exposure to neurotoxins, and other commonsense actions should be an explicit component of brain health.

Comments

Hi Margarita, thanks for the message. The problem is that the treatments *may* hurt human beings. Anti-amyloid research studies (specifically the amyloid vaccine) have been discontinued because the drugs were literally killing people by causing encephalitis, or swelling of the brain.

Perhaps the pre-symptomatic blocking of amyloid would be more effective, since that would occur further downstream, but this remains to be seen. They are doing studies in a region in Columbia disproportionately affected by early onset AD to determine this.

But as of now, the treatments are ineffectual and potentially dangerous, so it’s hard to find any reason to continue being optimistic about them.
take care,
Danny